生存素对过敏性鼻炎鼻黏膜组织中CD4^+T细胞凋亡的调控及其机理  

Regulatory effects of survivin on CD4^+T cell apoptosis in nasal mucosa of allergic rhinitis and its mechanism

作　　者：高照慧 孙子慧 宋梦婷 薛金梅[2] 赵长青[2] 杨平常[3] GAO Zhaohui;SUN Zihui;SONG Mengting;XUE Jinmei;ZHAO Changqing;YANG Pingchang(Second Clinical Medical School,Shanxi Medical University,Taiyuan 030001,China;Department of Otolaryngology,Head&Neck Surgery,Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Research Center of Allergy&Immunology,Shenzhen University School of Medicine,Shenzhen 518060,China)

机构地区：[1]山西医科大学第二临床医学院,太原030001 [2]山西医科大学第二医院耳鼻咽喉头颈外科 [3]深圳大学过敏反应与免疫学重点实验室,518060

出　　处：《免疫学杂志》2019年第12期1081-1087,共7页Immunological Journal

基　　金：国家自然基金（81970865）;山西省科技厅重点研发项目（201803D31117）;山西省人社厅留学人员科技活动择优资助项目（201706)

摘　　要：目的通过检测季节性过敏性鼻炎(seasonal allergic rhinitis,SAR)患者鼻黏膜CD4+T细胞生存素、Fas表达水平及其凋亡细胞频率,探讨生存素对SAR患者鼻黏膜CD4+T细胞凋亡过程的调控作用及其机理。方法收集2016年1月至2017年1月期间来我院就诊的30例SAR患者(SAR组)及30例单纯鼻中隔患者(对照组)的下鼻甲黏膜,分离提取得到CD4+T细胞,Western blot、RT-qPCR法检测CD4+T细胞生存素的表达水平;经AICD激活剂处理2组CD4+T细胞后,流式细胞术检测凋亡细胞的频率,Western blot、RT-qPCR法检测Fas表达水平;采用生存素shRNA处理SAR组鼻黏膜CD4+T细胞,使生存素基因沉默,检测凋亡细胞的频率、Fas表达水平;采用生存素质粒转染对照组鼻黏膜CD4+T细胞,使生存素过表达,检测凋亡细胞的频率、Fas表达水平。结果 SAR组鼻黏膜CD4+T细胞生存素表达水平明显高于对照组(P<0.05)。经AICD激活剂处理后,SAR组鼻黏膜CD4+T细胞凋亡细胞频率、Fas表达水平显著低于对照组(P<0.05)。生存素shRNA处理SAR组鼻黏膜CD4+T细胞后,其凋亡细胞频率、Fas表达水平明显高于shRNA-NC(P<0.05)。生存素质粒转染对照组鼻黏膜CD4+T细胞后,凋亡细胞的频率、Fas表达水平明显低于对照质粒(P<0.01)。结论与对照组相比,生存素在SAR患者鼻黏膜组织CD4+T细胞中高表达,其可能通过下调CD4+T细胞表面Fas的表达,抑制CD4+T细胞AICD过程,使活化的CD4+T细胞在鼻黏膜中持续存在,参与AR中Th2异常优势的维持。This study was performed to investigate the mechanism of survivin affecting the apoptosis of CD4+T cells in nasal mucosa of SAR patients by measuring the dynamic changes of Fas and survivin expression. RT-qPCR and Western blot were used to detect the expression of survivin and Fas in CD4+T cells, while flow cytometry assay was performed to detect the apoptosis of CD4+T cells in nasal mucosa of SAR patients. Data showed that the expression of survivin was significantly upregulated in CD4+T cells, while the expression of Fas and the frequency of apoptotic cells decreased in CD4+T cells of nasal mucosa of SAR patients. Survivin knockdown significantly increased the expression of Fas and the frequency of apoptotic cells. Survivin overexpression significantly decreased the expression of Fas and the frequency of apoptotic cells. In conclusion, survivin plays a critical role in the pathogenesis of allergic rhinitis by facilitating the biased Th2 polarization and compromising the AICD of CD4+T cells. Survivin may be a novel therapeutic target in the treatment of allergic rhinitis.

关 键 词：生存素 过敏性鼻炎 鼻黏膜 CD4+T细胞 AICD 

分 类 号：R765.21[医药卫生—耳鼻咽喉科]